PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.

The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1α and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N...

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Main Authors: Shafee, Norazizah, Kaluz, Stefan, Ru, Ning, Stanbridge, Eric John
Format: Article
Language:English
Published: Elsevier 2009
Online Access:http://psasir.upm.edu.my/id/eprint/16221/
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author Shafee, Norazizah
Kaluz, Stefan
Ru, Ning
Stanbridge, Eric John
author_facet Shafee, Norazizah
Kaluz, Stefan
Ru, Ning
Stanbridge, Eric John
author_sort Shafee, Norazizah
building UPM Institutional Repository
collection Online Access
description The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1α and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3Kact cells increased HIF-1α but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity.
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institution Universiti Putra Malaysia
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spelling upm-162212014-02-11T04:41:11Z http://psasir.upm.edu.my/id/eprint/16221/ PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines. Shafee, Norazizah Kaluz, Stefan Ru, Ning Stanbridge, Eric John The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1α and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3Kact cells increased HIF-1α but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity. Elsevier 2009-09-08 Article PeerReviewed Shafee, Norazizah and Kaluz, Stefan and Ru, Ning and Stanbridge, Eric John (2009) PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines. Cancer Letters, 282 (1). pp. 109-115. ISSN 0304-3835; ESSN: 1872-7980 10.1016/j.canlet.2009.03.004 English
spellingShingle Shafee, Norazizah
Kaluz, Stefan
Ru, Ning
Stanbridge, Eric John
PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title_full PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title_fullStr PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title_full_unstemmed PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title_short PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CAIX and VEGF, in human cancer cell lines.
title_sort pi3k/akt activity has variable cell-specific effects on expression of hif target genes, caix and vegf, in human cancer cell lines.
url http://psasir.upm.edu.my/id/eprint/16221/
http://psasir.upm.edu.my/id/eprint/16221/